Investigation of MicroRNA-134 as a Target against Seizures and SUDEP in a Mouse Model of Dravet Syndrome.pdf (1.7 MB)
Investigation of MicroRNA-134 as a target against seizures and SUDEP in a mouse model of Dravet syndrome
journal contributionposted on 2023-10-25, 10:20 authored by Rogério Gerbatin, Joana Augusto, Gareth Morris, Aoife Campbell, Jesper Worm, Elena Langa, Cristina Ruedell ReschkeCristina Ruedell Reschke, David HenshallDavid Henshall
Dravet syndrome (DS) is a catastrophic form of pediatric epilepsy mainly caused by noninherited mutations in the SCN1A gene. DS patients suffer severe and life-threatening focal and generalized seizures which are often refractory to available anti-seizure medication. Antisense oligonucleotides (ASOs) based approaches may offer treatment opportunities in DS. MicroRNAs are short noncoding RNAs that play a key role in brain structure and function by post-transcriptionally regulating gene expression, including ion channels. Inhibiting miRNA-134 (miR-134) using an antimiR ASO (Ant-134) has been shown to reduce evoked seizures in juvenile and adult mice and reduce epilepsy development in models of focal epilepsy. The present study investigated the levels of miR-134 and whether Ant-134 could protect against hyperthermia-induced seizures, spontaneous seizures and mortality (SUDEP) in F1.Scn1a(1/)tm1kea mice. At P17, animals were intracerebroventricular in-jected with 0.1–1 nmol of Ant-134 and subject to a hyperthermia challenge at postnatal day (P)18. A second cohort of P21 F1.Scn1a(1/)tm1kea mice received Ant-134 and were followed by video and EEG monitoring until P28 to track the incidence of spontaneous seizures and SUDEP. Hippocampal and cortical levels of miR-134 were similar between wild-type (WT) and F1.Scn1a(1/)tm1kea mice. Moreover, Ant-134 had no effect on hyperthermia-induced seizures, spontaneous seizures and SUDEP incidence were unchanged in Ant-134-treated DS mice. These findings suggest that targeting miR-134 does not have therapeutic applications in DS.
Science Foundation Ireland (SFI) Grant 16/ RC/3948
European Regional Development Fund
Charitable Infirmary Charitable Trust Grant 108
Marie Skłodowska-Curie Actions Grant H2020-MSCA-IF-2018 840262
Emerging Leader Fellowship Award F2102
FutureNeuro industry partners
F. Hoffman-La Roche Ltd.
CommentsThe original article is available at https://www.eneuro.org/
Published CitationGerbatin RR. et al. Investigation of MicroRNA-134 as a target against seizures and SUDEP in a mouse model of Dravet syndrome. eNeuro. 2022;9(5):ENEURO.0112-22.2022.
Publication Date9 September 2022
- FutureNeuro Centre
- Physiology and Medical Physics
- School of Pharmacy and Biomolecular Sciences
- Neurological and Psychiatric Disorders
PublisherSociety for Neuroscience
- Published Version (Version of Record)